BACKGROUND AND AIM: Although chronic liver disease is associated with secondary sarcopenia, the effect of primary disease treatment (hepatitis C virus elimination) on the skeletal muscle is unclear. This study aimed to determine the effect of a sustained virologic response at 24 weeks following direct-acting antiviral therapy on the skeletal muscle in hepatitis C virus-infected patients. METHODS: Hepatitis C virus-infected patients treated with direct-acting antivirals between 2014 and 2017 in our hospital were included. We evaluated the skeletal muscle index and intramuscular adipose tissue content at the third lumbar vertebra on abdominal computed tomography and compared the rate of change in the skeletal muscle index per year and intramuscular adipose tissue content per year before and after direct-acting antiviral treatment. RESULTS: Ninety-two patients participated. At sustained virologic response at 24 weeks, liver test results, including fibrosis marker levels, were significantly improved compared to those before direct-acting antiviral treatment. Skeletal muscle index measured before direct-acting antiviral treatment initiation was significantly lower than that at the first computed tomography scan. However, no significant change was found between the skeletal muscle index at the second computed tomography scan and final follow up. The rate of change in skeletal muscle index measured after direct-acting antiviral treatment was significantly higher than that before direct-acting antiviral treatment (-0.07 vs -0.99% per year). There was no significant difference between the change in intramuscular adipose tissue content before and after direct-acting antiviral treatment. CONCLUSIONS: Viral eradication by direct-acting antiviral treatment improved the liver function and suppressed skeletal muscle loss in hepatitis C virus-infected patients.